The overall objectives of this project are the definition and elucidation of the anti-infarction effect of chronic cardiac denervation. Work completed to date has shown that: (1) Following coronary ligation, infarct size is much less in the dog heart which had been chronically (2-3 wk) denervated. (2) The reduction in infarct size is associated with a reduction resting coronary blood flow before occlusion and an increased perfusion of ischemic myocardium after coronary occlusion. (3) The increased ischemic perfusion is associated with a reduction in coronary collateral resistances. (4) The reduced collateral resistances may be associated with coronary collateral vessel proliferation. And (5) the reduced pre-occlusion blood flow in the chronically denervated heart is associated with a reduced myocardial oxygen consumption over a wide range of cardiac work loads. These results imply that the anti-infarction effect may be due to both a reduced blood flow demand and to an increased collateral blood flow. The work further proposed will re-examine the effect of chronic denervation on myocardial infarction. While previous work showed a reduction in infarct size, present work will use the S-T segment and CPK techniques to examine the effects of chronic denervation on infarct severity.